The effects of indanyloxyacetic acid (mk 196) on electrolyte excretion in the rat kidney.

Abstract

A substituted derivative of ethacrynic acid, 6,7-dichloro-2-methyl-l-oxo-phenyl-5-indanyloxyacetic acid (MK 196), has been shown in preliminary studies to be a potent uricosuric and diuretic agent in the rat and monkey (1, 2). Prior studies from this laboratory have localized the nephron site of inhibition of urate reabsorption to the proximal convoluted tubule. The reabsorption of sodium in the proximal tubule, however, is not affected by MK 196, and the sodium diuresis results from impaired reabsorption in the ascending limb of the loop of Henle (1). The current studies were undertaken to examine further the changes in electrolyte excretion induced by this agent and to gain additional inferential information on the nephron site of action. Methods. Clearance studies. Male Sprague-Dawley rats weighing 200 to 400 g were used in all studies. Animals were anesthetized with Inactin (Promonta, Hamburg, Germany), 100 mg/kg body wt injected in-traperitoneally, and prepared for clearance studies as previously described (3). A solution of isotonic saline containing [methoxy-3H]inulin (25 μCi/ml) was infused at a rate of 1.2 ml/hr for the duration of the experiment. MK 196 was dissolved in distilled water containing an equal concentration of sodium bicarbonate and infused in a dose of 50 mg/kg body wt/hr in a volume of 1.2 ml/ hr. Control animals received the same solution without the drug. In the experimental animals, urinary losses of sodium and water were replaced with a volume of isotonic saline equal to the urine flow rate. Hematocrits were measured before and after the study to ensure the adequacy of volume replacement. After 60 to 90 min of equilibration, blood and urine samples were obtained. Free water clearance and reabsorption studies. Studies were performed in a separate group of animals that were lightly anesthetized with ether for placement of catheters, placed in restraining cages, and allowed to awaken.